Centre selection for clinical trials and the generalisability of results: a mixed methods study.

BACKGROUND: The rationale for centre selection in randomised controlled trials (RCTs) is often unclear but may have important implications for the generalisability of trial results. The aims of this study were to evaluate the factors which currently influence centre selection in RCTs and consider how generalisability considerations inform current and optimal practice. METHODS AND FINDINGS: Mixed methods approach consisting of a systematic review and meta-summary of centre selection criteria reported in RCT protocols funded by the UK National Institute of Health Research (NIHR) initiated between January 2005-January 2012; and an online survey on the topic of current and optimal centre selection, distributed to professionals in the 48 UK Clinical Trials Units and 10 NIHR Research Design Services. The survey design was informed by the systematic review and by two focus groups conducted with trialists at the Birmingham Centre for Clinical Trials. 129 trial protocols were included in the systematic review, with a total target sample size in excess of 317,000 participants. The meta-summary identified 53 unique centre selection criteria. 78 protocols (60%) provided at least one criterion for centre selection, but only 31 (24%) protocols explicitly acknowledged generalisability. This is consistent with the survey findings (n = 70), where less than a third of participants reported generalisability as a key driver of centre selection in current practice. This contrasts with trialists' views on optimal practice, where generalisability in terms of clinical practice, population characteristics and economic results were prime considerations for 60% (n = 42), 57% (n = 40) and 46% (n = 32) of respondents, respectively. CONCLUSIONS: Centres are rarely enrolled in RCTs with an explicit view to external validity, although trialists acknowledge that incorporating generalisability in centre selection should ideally be more prominent. There is a need to operationalize 'generalisability' and incorporate it at the design stage of RCTs so that results are readily transferable to 'real world' practice

Treatment effects may remain the same even when trial participants differed from the target population

Objective RCTs have been criticised for lacking external validity. We assessed whether a trial in people with type I diabetes mellitus (T1DM) mirrored the wider population, and applied sample-weighting methods to assess the impact of differences on our trial's findings. Study design and setting The REPOSE trial was nested within a large UK cohort capturing demographic, clinical and quality of life (QoL) data for people with T1DM undergoing structured diabetes-specific education. We firstly assessed whether our RCT participants were comparable to this cohort using propensity score modelling. Following this we re-weighted the trial population to better match the wider cohort and re-estimated the treatment effect. Results Trial participants differed from the cohort in regards to sex, weight, HbA1c and also QoL and satisfaction with current treatment. Nevertheless, the treatment effects derived from alternative model weightings were similar to that of the original RCT. Conclusions Our RCT participants differed in composition to the wider population but the original findings were unaffected by sampling adjustments. We encourage investigators take steps to address criticisms of generalisability, but doing so is problematic: external data, even if available, may contain limited information and analyses can be susceptible to model misspecification

COVID-19 Pandemic Significantly Decreases Acute Surgical Complaints.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic significantly reduced elective surgery in the United States, but the impact of COVID-19 on acute surgical complaints and acute care surgery is unknown. STUDY DESIGN: A retrospective review was performed of all surgical consults at the Hospital of the University of Pennsylvania in the 30 days prior to and 30 days following confirmation of the first COVID-19 patient at the institution. Consults to all divisions within general surgery were included. RESULTS: Total surgical consult volume decreased by 43% in the post-COVID-19 period, with a significant reduction in the median daily consult volume from 14 to 8 ( CONCLUSION: The COVID-19 pandemic significantly altered the landscape of acute surgical complaints at our large academic hospital. An appreciation of these trends may be helpful to other Departments of Surgery around the country as they deploy staff and allocate resources in the COVID-19 era

Reynolds Number Effects On The Performance Of Ailerons And Spoilers

The influence of Reynolds number on the performance of outboard spoilers and ailerons was investigated on a generic subsonic transport configuration in the National Transonic Facility over a chord Reynolds number range from 3 to 30 million and a Mach number range from 0.70 to 0.94. Spoiler deflection angles of 0, 10, and 20 degrees and aileron deflection angles of-10, 0, and 10 degrees were tested. Aeroelastic effects were minimized by testing at constant normalized dynamic pressure conditions over intermediate Reynolds number ranges. Results indicated that the increment in rolling moment due to spoiler deflection generally becomes more negative as the Reynolds number increases from 310 6 to 2210 6 with only small changes between Reynolds numbers of 2210 6 and 3010 6 . The change in the increment in rolling moment coefficient with Reynolds number for the aileron deflected configuration is generally small with a general trend of increasing magnitude with increasing Reynolds numb..